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An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

Published on: December 3, 2020

Moving from basic toward systems pharmacodynamic models.

William J Jusko¹

¹Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, New York 14214, USA. wjjusko@buffalo.edu

Journal of Pharmaceutical Sciences

|May 18, 2013

Summary

This summary is machine-generated.

Pharmacokinetic-pharmacodynamic (PK/PD) models, built on drug action mechanisms, can be extended to complex physiological processes. These models integrate molecular to whole-body functions, offering advantages for systems biology approaches.

Keywords:

dose response indirect response models mathematical model pharmacodynamics pharmacokinetics pharmacometrics preclinical pharmacokinetics systems pharmacology

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Area of Science:

Pharmacology and Systems Biology
Mechanistic Pharmacokinetic-Pharmacodynamic (PK/PD) Modeling

Background:

Classical pharmacology provides foundations for mechanistic PK/PD models.
These models are based on drug action mechanisms and physiological turnover processes.
Existing models can be adapted to incorporate complexities like drug tolerance.

Purpose of the Study:

To demonstrate the extension of basic PK/PD models into enhanced systems models.
To illustrate the integration of molecular to whole-body processes using corticosteroid models.
To discuss the benefits and challenges of advancing PK/PD modeling toward systems approaches.

Main Methods:

Development and application of mechanistic pharmacokinetic-pharmacodynamic (PK/PD) models.
Extension of basic PK/PD models to incorporate physiological complexities and tolerance.
Integration of models across different biological scales (molecular to whole-body).

Main Results:

Demonstrated the utility of PK/PD models as building blocks for enhanced systems models.
Corticosteroid models exemplified horizontal and vertical integration of biological processes.
Identified potential advantages and challenges in transitioning PK/PD to systems models.

Conclusions:

Mechanistic PK/PD models are versatile and extensible for complex biological systems.
Integration across biological scales is feasible and beneficial for comprehensive modeling.
Further development of PK/PD toward systems models holds significant promise for pharmacology.